Lectins are involved in a wide variety of cellular functions, many of which are related to their only common feature, the ability to bind carbohydrates specifically and reversibly, and to agglutinate cells reviewed in (1)!. Animal lectins are classified as C-lectins, which are Ca.sup.2+ -dependent and are structurally related to the asialoglycoprotein receptor, and galectins, previously known as S-type lectins, which are thiol-dependent and specifically bind .beta.-galactoside residues. In mammals, four galectin types have been sequenced and characterized, and there is evidence for the existence of other relatives (2,3). All known members of this family lack a signal peptide, are found in the cytosol, and are isolated as soluble proteins. However, there is evidence that some members are externalized by an atypical secretory mechanism.
Galectins require fulfillment of two criteria: affinity for .beta.-galactosides and significant sequence similarity in the carbohydrate recognition domain (CRD) (4), the relevant amino acids residues of which have been determined by X-ray crystallography (5). Galectin-1 and -2 are homodimers with subunit molecular weight of .apprxeq.14 kDa, that are not subjected to post-translational modifications (6). Galectin-1 is found in the extracellular matrix and has been shown to interact with laminin (7). The function of galectin-1 and -2 is not yet fully understood, although there is evidence that they might be involved in regulation of cell growth (8); cell adhesion (7); cell transformation (9); and embryogenesis (10).
Larger galectins (galectin-3) (previously known as CBP-35, Mac-2, RL-29) do exist ((11) and references therein). These are monomeric 29-35 kDa mosaic proteins, composed of an N-terminal half made of tandem repeats characteristic of the collagen gene superfamily, and a C-terminal half homologous to galectins-1 and -2 (11). Galectin-3 also binds laminin, and is implicated as component of growth regulatory systems; mediator of cell--cell and cell-matrix interactions; modulator of immune response; marker of neoplastic transformation, and indicator for metastatic potential of melanoma cells.
Galectin-4 was cloned from rat intestine (12), and an homologous protein was cloned from nematode (13). Galectin-4 is a monomer with molecular mass of 36 kDa. It contains tandem domains of .apprxeq.140 amino-acids each, homologous to galectin-1 and -2, that are separated by a link region (12). The function of galectin-4 is presently unknown.
Galectins may functionally substitute each other. The absence of any major phenotypic abnormalities in mice carrying a null mutation in the gene encoding galectin-1, suggests that other protein(s), presumably galectin-3, are capable of functionally substituting for galectin-1, at least at early stages of embryogenesis.
It is an object of the present invention to provide the cloning of a cDNA encoding for a novel protein that we term galectin-8. Galectin-8 has the characteristic properties of other galectins (2,3), and it is structurally related (34% identity) to rat galectin-4 (12).